RASi Therapy Beneficial in Patients With HF Managed With an LV Assist Device

Renin-angiotensin system inhibitor (RASi) treatment is associated with a decreased risk for renal outcomes and mortality in patients with heart failure (HF) supported by a left ventricular assist device (LVAD) compared with patients who are not receiving RASi. These findings were published in Clinical Research in Cardiology.

The retrospective, observational study used data from INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support), which includes North American adults who received a Food and Drug Administration-approved mechanical circulatory support device related to advanced HF.

Participants were aged 18 years or older and had their first permanent continuous flow-LVAD device implanted from 2006 to 2017, and they were followed for 3 months or longer after LVAD implantation. All patients also had estimated glomerular filtration rate (eGFR) of 30 mL/ min/1.73 m² or higher at 3 months after LVAD implantation.

The main outcome was a composite of renal event and all-cause mortality, and the primary exposure was RASi therapy at study initiation and during follow-up. A renal event was a composite of doubling serum creatinine, eGFR decrease of 40% or more, or need for dialysis.

A total of 6448 patients (mean age, 57.3 [SD, 12.9] years; 79.2% men) were included. A majority were receiving RASi therapy 3 months after LVAD implantation (53.6% vs 46.4% who were not).

After a median follow-up of 12.7 months (IQR, 19.8 months), 1632 patients had the composite outcome. At 60 months, the unadjusted survival estimate for the composite outcome for participants who received RASi was 39.4% (95% CI, 35.0-44.4) vs 33.7% (95% CI, 29.9-38.0) for those who did not receive RASi (P <.001). When the 2 groups were compared separately, significant differences also were observed for renal outcomes (75.7% [95% CI, 71.0-80.7] vs 72.9% [95% CI, 68.4-77.6]) and all-cause mortality (48.3% [95% CI, 43.9-53.3] vs 42.0% [95% CI, 37.9-46.5]).

RASi treatment was associated with a lower risk for the composite outcome, as a significant association was found in the unadjusted and multivariable-adjusted models (model 1: hazard ratio [HR], 0.59; 95% CI, 0.53-0.65; P <.001; model 2: HR, 0.61; 95% CI, 0.55-0.68; P <.001). A significant association also was confirmed for renal outcomes (model 2: HR, 0.74; 95% CI, 0.61-0.89; P =.002) and all-cause mortality (model 2: HR, 0.56; 95% CI, 0.50-0.63; P <.001).

A significant interaction was found regarding the composite outcome in participants who were younger than age 65 years (P for interaction =.005).

Among several limitations, INTERMACS did not include data on whether HF was ischemic or not or information that may have been relevant to the therapeutic effects of RASi. Also, patient allocation to RASi treatment was not randomized, the criteria for allocation are not provided, and the dosages or adherence to RASi are unknown. Furthermore, the researchers cannot rule out that RASi treatment is associated with better access to care and follow-up, which could have affected the results.

“…RASi therapy demonstrated a beneficial role on survival and kidney function over time in patients with normal or mild impaired renal function, reducing the risk of ESKD,” the study authors wrote. “Therefore, we believe that despite the lack of RCTs on this subject, the effect of RASi in this particular context should be encouraged.”

Disclosure: One of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.